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The FLT4 gene plays an important role in the onset and progression of obesity and is involved in the structure and function of lymphatic vessels. By inducing a mouse obesity model with a high-fat diet and knocking out the FLT4 gene, which is associated with lymphatic vessel growth in mice, FLT4+/− mice were found to be susceptible to high-fat diet-induced obesity, with significant accumulation of visceral fat. BODIPY™ FL C 16 imaging revealed dilated and branched mesenteric lymphatic vessels in FLT4+/− mice. Immunofluorescence staining showed that FLT4+/− exacerbated the morphological abnormalities of lymphatic vessels and submucosal lymphatic vessels in visceral adipose tissue of obese mice, accompanied by macrophage infiltration around lymphatic vessels. In addition, FLT4 knock down increased the proportion of M1-type macrophages in the adipose tissue of the epididymis, indicating significant chronic inflammation in FLT4+/− obese mice. These findings provide new evidence for the involvement of lymphatic vessel morphological abnormalities in the onset and progression of obesity and highlight the importance of further investigation of FLT4 to better understand the mechanism of HFD-induced obesity and to develop related treatments. • Wild-type hyper-fat mice were obese and developed mesenteric lymphangiectasia. • On a high-fat diet, FLT4+/− mice gained more weight and developed abnormal glucose tolerance than wild-type mice. • In obese FLT4+/− mice, fat accumulated in the mesentery, and lymphatic vessels increased in diameter and branching. • Obese FLT4+/- mice showed macrophage accumulation around mesenteric and epididymal adipose tissue lymphatic vessels. [ABSTRACT FROM AUTHOR]

Abstract Adipogenesis is one of the key processes during obesity development. Better understanding of this process could advance our knowledge on obesity and its treatment. Transcription factors (TFs) are master regulators during adipogenesis, however, a system-wide analysis of TFs dynamic proteome during adipogenesis is lacking. Here, we profiled 472 TFs and systematically elucidated their roles during the first 7 days of adipogenesis of human adipose-derived stem cells (hADSCs) on proteome scale. We identified two main and four sub-phases during adipogenesis. The commitment phase (0 h–8 h) mainly mediated stem cell proliferation, differentiation and chromatin remodeling, in which proteins of SWI/SNF family are the key centroid nodes. The determination phase (1D-7D) predominately regulated fat cell differentiation and response to lipid and oxygen, which could be associated with terminal differentiation of adipocyte and responsible for maturation. PPARγ, CREB1 and MYC are the centroid nodes of this phase. Remarkably, we identified and verified three TFs (BATF3, MAFF and MXD4) as novel regulators of adipogenesis, whose over-expression could inhibit adipogenesis of hADSCs in vitro. Overall, our study provided a valuable TFs resource to understand the complex process of adipogenesis. Highlights • Systematically depicted dynamic profiles of TFs during adipogenesis of hADSCs at proteome level. • Divided adipogenesis of hADSCs into two main and four sub-stages via dynamic proteome patterns of TFs. • Revealed featured biological responses during different stages of adipogenesis and figured out critical regulatory TFs. • Proposed three novel regulatory TFs (MAFF, BATF3 and MXD4), whose over-expression could inhibit adipogenesis of hADSCs. [ABSTRACT FROM AUTHOR]

Highlights: [•] HOXA7 regulates MCF7 cell proliferation. [•] HOXA7 up-regulates ERα expression. [•] HOXA7 mediates estrogen-induced MCF7 cell proliferation. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro , but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment. • The first report about protein kinase posttranslational function on occurrence PCOS. • CK2α-AR axis promotes AR and ovulation related genes excessive expression. • CK2α promotes KGN cell line proliferation and inhibits apoptosis. • CK2α-AR pathway may serve as a therapeutic target against PCOS. [ABSTRACT FROM AUTHOR]

Inflammatory mediators and adhesion molecules have been implicated in a variety of diseases including atherosclerosis. As both the mediator-releasing and targeted cells, vascular endothelial cells play key role in pathological processes. NF-κB signaling regulates a cluster of inflammatory factors in LPS-activated vascular endothelial cells but the underlying mechanisms remain largely unknown. Here, we investigated the epigenetic regulation of LPS upon the expression of inflammatory mediators and adhesion molecules. We found that LPS treatment promoted jmjd3 expression, enhanced Jmjd3 nuclear accumulation in human vascular endothelial cells. In addition, LPS enhanced the demethylation of H3K27me3, a specific substrate of Jmjd3. LPS treatment recruited Jmjd3 and NF-κB to the promoter region of target genes, suggesting Jmjd3 synergizes with NF-κB to activate the expression of target genes. We further found that Jmjd3 attenuated the methylation status in promoter region of target genes, culminating in target gene expression. Our findings unveil epigenetic regulations of LPS upon NF-κB pathway and identify Jmjd3 as a critical modulator of NF-κB pathway and potential therapeutic target for NF-κB related diseases including atherosclerosis. [ABSTRACT FROM AUTHOR]